Randomized Controlled Trial

. 2018 Jul 9;18(1):225.

doi: 10.1186/s12887-018-1200-1.

The BabySeq project: implementing genomic sequencing in newborns

Ingrid A Holm^{1

2}, Pankaj B Agrawal^{3

4

5}, Ozge Ceyhan-Birsoy^{6

7

8}, Kurt D Christensen^{9

10}, Shawn Fayer⁹, Leslie A Frankel^{11

12}, Casie A Genetti³, Joel B Krier^{9

10}, Rebecca C LaMay⁹, Harvey L Levy^{3

4}, Amy L McGuire¹¹, Richard B Parad^{4

5

13}, Peter J Park^{9

14}, Stacey Pereira¹¹, Heidi L Rehm^{6

7

15}, Talia S Schwartz³, Susan E Waisbren^{3

4}, Timothy W Yu^{3

4

15}; BabySeq Project Team; Robert C Green^{9

10

15}, Alan H Beggs^{16

17}

Collaborators, Affiliations

Collaborators

BabySeq Project Team:
Pankaj B Agrawal, Alan H Beggs, Wendi N Betting, Carrie L Blout, Ozge Ceyhan-Birsoy, Kurt D Christensen, Pamela Diamond, Dmitry Dukhovny, Kathryn E Dunn, Shawn Fayer, Leslie A Frankel, Casie A Genetti, Chet Graham, Robert C Green, Amanda M Gutierrez, Maegan Harden, Margaret H Helm, Lillian Hoffman-Andrews, Ingrid A Holm, Joel B Krier, Matthew S Lebo, Kaitlyn B Lee, Harvey L Levy, Xingquan Lu, Sarah S Kalia, Kalotina Machini, Amy L McGuire, Jaclyn B Murry, Medha Naik, Tiffany Nguyen, Richard B Parad, Hayley A Peoples, Stacey Pereira, Devan Petersen, Uma Ramamurthy, Vivek Ramanathan, Heidi L Rehm, Amy Roberts, Jill O Robinson, Serguei Roumiantsev, Talia S Schwartz, Eleanor B Steffens, Meghan C Towne, Tina K Truong, Grace E VanNoy, Susan E Waisbren, Caroline M Weipert, Timothy W Yu

Affiliations

¹ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. ingrid.holm@childrens.harvard.edu.
² Department of Pediatrics, Harvard Medical School, Boston, MA, USA. ingrid.holm@childrens.harvard.edu.
³ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
⁴ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁵ Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
⁶ Laboratory for Molecular Medicine, Partners Healthcare Personalized Medicine, Cambridge, MA, USA.
⁷ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁰ Harvard Medical School, Boston, MA, USA.
¹¹ Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX, USA.
¹² Department of Psychological, Health and Learning Sciences, University of Houston College of Education, Houston, TX, USA.
¹³ Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁴ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
¹⁵ The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁶ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. Beggs@enders.tch.harvard.edu.
¹⁷ Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Beggs@enders.tch.harvard.edu.

PMID: 29986673
PMCID: PMC6038274
DOI: 10.1186/s12887-018-1200-1

Randomized Controlled Trial

The BabySeq project: implementing genomic sequencing in newborns

Ingrid A Holm et al. BMC Pediatr. 2018.

. 2018 Jul 9;18(1):225.

doi: 10.1186/s12887-018-1200-1.

Authors

Collaborators

BabySeq Project Team:
Pankaj B Agrawal, Alan H Beggs, Wendi N Betting, Carrie L Blout, Ozge Ceyhan-Birsoy, Kurt D Christensen, Pamela Diamond, Dmitry Dukhovny, Kathryn E Dunn, Shawn Fayer, Leslie A Frankel, Casie A Genetti, Chet Graham, Robert C Green, Amanda M Gutierrez, Maegan Harden, Margaret H Helm, Lillian Hoffman-Andrews, Ingrid A Holm, Joel B Krier, Matthew S Lebo, Kaitlyn B Lee, Harvey L Levy, Xingquan Lu, Sarah S Kalia, Kalotina Machini, Amy L McGuire, Jaclyn B Murry, Medha Naik, Tiffany Nguyen, Richard B Parad, Hayley A Peoples, Stacey Pereira, Devan Petersen, Uma Ramamurthy, Vivek Ramanathan, Heidi L Rehm, Amy Roberts, Jill O Robinson, Serguei Roumiantsev, Talia S Schwartz, Eleanor B Steffens, Meghan C Towne, Tina K Truong, Grace E VanNoy, Susan E Waisbren, Caroline M Weipert, Timothy W Yu

Affiliations

¹ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. ingrid.holm@childrens.harvard.edu.
² Department of Pediatrics, Harvard Medical School, Boston, MA, USA. ingrid.holm@childrens.harvard.edu.
³ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA.
⁴ Department of Pediatrics, Harvard Medical School, Boston, MA, USA.
⁵ Division of Newborn Medicine, Boston Children's Hospital, Boston, MA, USA.
⁶ Laboratory for Molecular Medicine, Partners Healthcare Personalized Medicine, Cambridge, MA, USA.
⁷ Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁸ Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
⁹ Division of Genetics, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁰ Harvard Medical School, Boston, MA, USA.
¹¹ Center for Medical Ethics and Health Policy, Baylor College of Medicine, Houston, TX, USA.
¹² Department of Psychological, Health and Learning Sciences, University of Houston College of Education, Houston, TX, USA.
¹³ Department of Pediatric Newborn Medicine, Brigham and Women's Hospital, Boston, MA, USA.
¹⁴ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
¹⁵ The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
¹⁶ Division of Genetics and Genomics, The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA, USA. Beggs@enders.tch.harvard.edu.
¹⁷ Department of Pediatrics, Harvard Medical School, Boston, MA, USA. Beggs@enders.tch.harvard.edu.

PMID: 29986673
PMCID: PMC6038274
DOI: 10.1186/s12887-018-1200-1

Abstract

Background: The greatest opportunity for lifelong impact of genomic sequencing is during the newborn period. The "BabySeq Project" is a randomized trial that explores the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.

Methods: Families of newborns are enrolled from Boston Children's Hospital and Brigham and Women's Hospital nurseries, and half are randomized to receive genomic sequencing and a report that includes monogenic disease variants, recessive carrier variants for childhood onset or actionable disorders, and pharmacogenomic variants. All families participate in a disclosure session, which includes the return of results for those in the sequencing arm. Outcomes are collected through review of medical records and surveys of parents and health care providers and include the rationale for choice of genes and variants to report; what genomic data adds to the medical management of sick and healthy babies; and the medical, behavioral, and economic impacts of integrating genomic sequencing into the care of healthy and sick newborns.

Discussion: The BabySeq Project will provide empirical data about the risks, benefits and costs of newborn genomic sequencing and will inform policy decisions related to universal genomic screening of newborns.

Trial registration: The study is registered in ClinicalTrials.gov Identifier: NCT02422511 . Registration date: 10 April 2015.

Keywords: Ethical, legal, social implications; Methods; Newborn screening; Newborn sequencing; Randomized trial; Whole exome sequencing.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

The BCH, BWH, and BCM IRBs have approved this study. All parents provided consent for their child and themselves to participate in the study. All health care providers consented to the study by completing the survey, which constitutes consent.

Consent for publication

Not applicable.

Competing interests

Authors have declared competing interest as follows:

HLR is employed by Partners Healthcare and Broad Institute that offer fee-based clinical sequencing. TWY is a founder of and consultant for Claritas Genomics, a diagnostic company for children with complex genetic disorders. RCG receives compensation for speaking or consultation from AIA, GenePeeks, Helix, Illumina, Ohana, Prudential, and Veritas, and is co-founder and advisor to Genome Medical, Inc. IAH, PBA, OCB, KDC, SF, LAF, CAG, JBK, RCL, HLL, ALM, RBP, PJP, SP, TSS, SEW, and AHB declare no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

**Fig. 1**
BabySeq Study Design Overview

**Fig. 2**
BabySeq Parental and Physician Survey Timeline

See this image and copyright information in PMC

References

1. Green RC, Rehm HL, Kohane IS: Clinical genome sequencing. In: Genomic and Personalized Medicine.Volume 1, 2nd edn Edited by Ginsburg GS, Willard HF. San Diego: Elsevier Inc.; 2013: 102–122.
1. Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014;370:2418–2425. doi: 10.1056/NEJMra1312543. - DOI - PubMed
1. Medical genetics laboratories: Whole genome laboratory (WGL) [http://www.bcm.edu/geneticlabs/index.cfm?PMID=21319].
1. Jamuar SS, Tan EC: Clinical application of next-generation sequencing for Mendelian diseases. Hum Genomics. 2015; 9:10. 10.1186/s40246-015-0031-5. - PMC - PubMed
1. Dewey FE, Grove ME, Pan C, Goldstein BA, Bernstein JA, Chaib H, Merker JD, Goldfeder RL, Enns GM, David SP, et al. Clinical interpretation and implications of whole-genome sequencing. Jama. 2014;311(10):1035–1045. doi: 10.1001/jama.2014.1717. - DOI - PMC - PubMed

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The BabySeq project: implementing genomic sequencing in newborns

Collaborators

Affiliations

The BabySeq project: implementing genomic sequencing in newborns

Authors

Collaborators

Affiliations

Abstract

Conflict of interest statement

Ethics approval and consent to participate

Consent for publication

Competing interests

Publisher’s Note

Figures

References

Publication types

MeSH terms

Associated data

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Medical

Molecular Biology Databases

Miscellaneous